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Secrets of immune response illuminated in new study
Date:2/9/2012

rom the dendritic cell to the memory CD8+ T cell, triggering the release of IFN-λ. Figure 1 graphically describes this process.

In the current study, antigen-independent secretion of IFN-λ by memory CD8+ T cells was demonstrated in mice infected with the intracellular pathogen Salmonella Typhimurium. The response could be detected as soon as 2 hours post-infectionthe NOD-like receptors representing the earliest response to pathogenic invasion. Further, by using strains of S. Typhimurium deficient in flaggelin, the group showed impaired IFN-λ secretion by CD8+ T cells.

Intriguingly, the group also found a robust IFN-λ response when dendritic cells were presented with heat-killed S. Typhimurium or even with the injection of purified flaggelin alonepowerful evidence that the dendritic cell inflammasome assembled by the NOD-like receptor's sensing of flaggelin was sufficient to induce IFN-λ production in memory CD8+ T cells. This flaggelin-induced response was also demonstrated for two other pathogens: Yersinia and Pseudomonas.

The study also confirmed the hypothesis that production of IL-18 in dendritic cells, following inflammasome formation, generated the production of IFN-λ by attaching to a specific receptor-adaptor on the memory CD8+ T cells, which the group identified. The authors speculate that a particular inflammasome known as NAIP5 in splenic dendritic cells is responsible for sensing flaggelin and initiating the cascade of events leading to IFN-λ production in CD8+ T cells.

Previous research had suggested a mechanism for S. Typhimurium to transfer flagellin into the cell from the extracellular medium, through the pathogen's specific secretion system. This is considered critical, as many bacteria are non-pathogenic and indeed, important to the host. An inflammasome response to these so-called commensal bacteria could therefore have disastrous consequences, triggering an inappropriate auto-
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Contact: Joseph Caspermeyer
Joseph.Caspermeyer@asu.edu
Arizona State University
Source:Eurekalert  

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